Oximes amine hydrochlorides

Chill the concentrated solution of the amine hydrochloride in ice-water, and then cautiously with stirring add an excess of 20% aqueous sodium hydroxide solution to liberate the amine. Pour the mixture into a separating-funnel, and rinse out the flask or basin with ether into the funnel. Extract the mixture twice with ether (2 X25 ml.). Dry the united ether extracts over flake or powdered sodium hydroxide, preferably overnight. Distil the dry filtered extract from an apparatus similar to that used for the oxime when the ether has been removed, distil the amine slowly under water-pump pressure, using a capillary tube having a soda-lime guard - tube to ensure that only dry air free from carbon dioxide passes through the liquid. Collect the amine, b.p. 59-61°/12 mm. at atmospheric pressure it has b.p. 163-164°. Yield, 18 g. 

An assay method for benzaldehyde involves condensing benzaldehyde with hydroxyl amine hydrochloride to form an oxime. The released hydrochloric acid is then titrated. 

A mixture of 3 -hydroxypregna-5,l6-dien-20-one acetate (10 g), 70 ml of ethanol and 2 ml of methoxylamine is refluxed for 12 hr (Note methoxyl-amine hydrochloride leads to oxime formation). After cooling, another 1.75 ml of methoxylamine is added and the reaction is refluxed for another 12 hr. The solvent is removed in vacuo and the residue is dissolved in ether. Hydrogen chloride gas is passed into the ether solution and the white crystalline salt (113) is filtered off and washed with ether (85% yield crude mp 228-229°). 

Chloroaeetophenone oxime was prepared by a modification of the method described by Shriner, Fuson, and Curtin.5 A mixture of 100 g. (0.65 mole) of reagent-grade 4-chloroacetophenone, 300 ml. of water, 200 ml. of aqueous 10% sodium hydroxide, 50g. (0.72 mole) of hydroxyl-amine hydrochloride, and 500 ml. of ethanol is heated at reflux in a 2-1. round-bottomed flask for 2 hours. The crystals that separate on cooling in an ice bath are recovered by filtration and air dried. The product is added to approximately 1 1. of hexane, and the mixture is... 

The reactivity of the keto group is not influenced by the substitution the reaction of 3-(trifluoromethylmercapto)-2-butanone with hydroxyl-amine hydrochloride gives the corresponding oxime in good yield. Cyclization of diketones and keto esters to pyrazole derivatives succeeds by the well-known method using phenylhydrazine ... 

The acetoxime may be distilled by direct heating rather than by injection of steam when the prescribed quantities are taken, however, it will be found that the liquor becomes saturated with sodium sulfate at a point just before the expulsion of the oxime is complete, so that addition of water during the distillation is necessary. More rapid distillation can be obtained by the use of a current of steam, especially if a condensing receiver (Vol. II, pp. 80-82) be employed. The oxime can also, if desired, be isolated for hydrolysis by separation of the oily layer and extraction with benzene the resulting crude hydroxyl-amine hydrochloride is, however apt to be dark in color and to contain inorganic salts. 

Fig. 3.1.9 Mass spectra of succinylacetone. a,b Peaks I and II, with oximation (reagent hydroxyl-amine hydrochloride). The insert shows the characteristic appearance of the two chromatographic peaks [32] c-e see next page...

A. 4-Aaetylpyridine oxime. Hydroxyl amine hydrochloride (25.0 g, 0.36 mol) (Note 1) is dissolved in 50 mL of water, and the solution 1s added to 70 mL of 20K aqueous sodium hydroxide in a 500-mL Erlenmeyer flask. To this magnetically stirred solution 1s added at one time 4-acetyl pyridine (36.3 g, 0.30 mol) (Note 2) a precipitate forms rapidly. The reaction mixture is stirred at 0-5°C for 2 hr then the precipitate is collected by suction filtration and washed with 500 mL of cold water. 

Hydroxylamine hydrochloride (8) Hydroxyl amine, hydrochloride (9) (5470-11-1) 4-Acetyl pyridine oxime Ketone, methyl 4-pyridyl oxime (8) Ethanone, l-(4-pyridinyl)- oxime (9) (1194-99-6)... 

Benzotellurazole1 14.3 g (50 mmol) of 2-formylphenyl butyl tellurium, 3.8 g (55 mmol) of hydroxyl-amine hydrochloride, and 5.9 g (60 mmol) of fused potassium acetate are added to 100 ml of absolute ethanol and the mixture is heated under reflux with stirring for 2 h. The mixture is then concentrated, extracted with chloroform, and the extract is concentrated. The residue (the crude oxime) is added to a mixture of 50 ml of 85% phosphoric acid and 100 g of phosphorus pentoxide. This mixture is stirred and heated at 100° for 1 h, cooled, and poured into a mixture of ice and aqueous ammonia. The mixture is filtered, the solid is extracted with chloroform and the extract is dried and evaporated. The residue is recrystallized from methanol yield 4.6 g (40%) m.p. 173. ... 

Seventy grams (1.07 gram atoms) of zinc dust is added in small portions under a reflux condenser to a stirred solution of 40 g. (0.205 mole) of fluorenone oxime (p. 164) in 267 ml. of acetic acid and 13 ml. of water. The rate of addition of the zinc is such as to maintain an even, gentle reflux. The mixture is then refluxed for another hour by the application of heat, and this is followed by the addition of 400 ml. of water. The mixture is filtered and the residue extracted with 200 ml. of hot 5% acetic acid. The solution thus obtained is cooled and filtered, and the filtrate is mixed with an equal volume of concentrated hydrochloric acid and held at 0° for 12 hours. The precipitated amine hydrochloride is removed by filtration and treated with excess ammonium hydroxide solution, and the resulting free base is recrystallized from petroleum ether to give a 90% yield of 9-aminofluorene, m.p. 62-63 . 

Benzoin Oxime. 2-Hydroxy-l,2-diphenyiethanone Mime 2-hydroxy -2-phenylacetophenone oxime. C Hts-NOji mol wt 227.25. C 73.99%, H 5.76%, N 6.16%, O 14.08%. Two isomers occor a or anti and /S or syn. Both have been prepd from benzoin and hydroxyl amine hydrochloride. Prepn of a-form Werner, Detscheff, Ber. 38, 69 (1905) F. J. Welcher, Organic Analytical Reagents vol. Ill (Van Nosttand, New York, 1947) pp 239-251. Prepn of 3-form Werner, Detscheff, loc. cit, Configuration of a - and Worms Meisenheimer, Meis, Ber. 57, 289 (1924). 

A solution of the nitrile (or oxime) (1 mole) in 1-butanol (2300 ml) is heated to boiling in a 5-1 two-necked flask fitted with a wide condenser (2.5 x 100 cm), and sodium (161 g in 10-20-g portions) is then added during 20 min. When the reaction slackens, heating under reflux is continued until almost all the sodium is dissolved, then the solution is allowed to cool, water (1.5 1) is added, and the butanol and amine are distilled off (the distillate is tested for amine, and if necessary more water is added and distillation continued). The distillate is made weakly acidic and concentrated (to 300 ml), then water (500 ml) is again added and distillation is continued until no more butanol passes over. The resulting concentrated butanol-free solution of the amine hydrochloride is supersaturated with alkali, and the amine is separated (if necessary with addition of ether) and dried first with solid alkali and then with sodium, after which distillation affords the pure amine without forerun or subsequent fraction. (The reaction is said to fail if sodium containing 0.1-0.01 % of potassium is used.30)... 

Despite the powerful potential of the Neber rearrangement, it has been scarcely utilized in the total synthesis of complex natural products. The earliest such application was in Woodward s total synthesis of lysergic acid. Although not utilized in the successful route to this alkaloid, an early approach to the a-aminoketone (24) exploited the Neber rearrangement on compound 22. Preparation of the oxime (23) followed by rearrangement provided the amine hydrochloride 24 in good yield however, this compound was unstable as a free base and could not be processed further en route to lysergic acid. 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

Bei der Reduktion von Oximen mit Natrium-trithio-dihydrido-borat werden meist Gemische von Hydroxylamin und prim. Amin gebildet3. Natriumboranat/Silicagel reduziert Oxime in Benzol-Lo-sungzu Hydroxylamin - Boranen, die durch Salzsiiure in die N-Alky] - hydroxylamin-Hydrochloride iibergefiihrt werden4. 

B. 2-Methoxycyclooctanone oxime. In a 500-ml., three-necked, round-bottomed flask, fitted with a mechanical stirrer, a dropping funnel, and a reflux condenser equipped with a calcium chloride tube, is placed a solution of 53.5 g. (0.252 mole) of crude 2-chlorocyclooctanone oxime hydrochloride in 250 ml. of methanol. While cooling the vessel with running water, 60.7 g. of triethyl-amine (0.60 mole) is added dropwise during 40 minutes. The reaction temperature is kept below 50° and the reaction is continued for 30 minutes with stirring. After removal of methanol under reduced pressure using an efiicient rotatory evaporator, a light brown semisolid is obtained it is treated with 200 ml. of ether and 200 ml. of water to effect complete solution. The ether layer is separated and the aqueous layer is further extracted twice with ether. The combined ether solution is washed with saturated sodium chloride and dried over sodium sulfate. Removal of ether affords 42.8 g. of crude 2-methoxycyclooctanone oxime (Note 3) as a brown oil. 

Reaction of the a-hydroxyketone (+)-1402 with hydroxylamine hydrochloride gave the oxime (—)-1407 in 95% yield. A bis-methylation of (—)-1407 under phase transfer conditions afforded the corresponding dimethyl derivative (—)-1408. Stereoselective hydrogenation of (—)-1408 using H2/Pt02 led to the amine... 

Further evidence for the above chemical shift rule was collected subsequently for systems such as oximes, oxime hydrochlorides, hydrazones, hydrazonium iodides, and imines 287, as well as for A -(2-cyclohexen-l-ylidene)amines (enimines) 288. Similar to enol ethers267, electric-field effects are held responsible287. 

Amide reduction with lithium aluminum hydride, 39, 19 Amine oxide formation, 39, 40 Amine oxide pyrolysis, 39, 41, 42 -Aminoacetanilide, 39, 1 Amino adds, synthesis of, 30, 7 2-Amino-4-anilino-6-(chloro-METHYl) -S-TRIAZINE, 38, 1 -Aminobenzaldehyde, 31, 6 hydrazone, 31, 7 oxime, 31, 7 phenylhydrazone, 31, 7 > -Aminobenzoic add, 36, 95 2-Aminobenzophenone, 32, 8 c-Aminocaproic acid, 32, 13 6-Aminocaproic acid hydrochloride,... 

Synthesis (Freed and Potoski (American Home), 1971 Freed, 1973 Kleemann et al., 1999,) Dezocine is prepared through the following sequence The condensation of 1-methyl-7-methoxy-2-tetralone with 1,5-di-bromopentane by means of NaH or potassium tertbutylate affords 1 -(5-bromopentyl)-1 -methyl-7-methoxy-2-tetralone this product is cyclized with NaH to give 5-methyl-3-methoxy-5,6,7,8,9,10,11,12-octahydro-5,11 -methano-benzocyclodecen-13-one i. The ketone i, by reaction with hydroxylamine hydrochloride in pyridine, is converted into its oxime ii, which is reduced with H2 over Raney Ni to a mixture of isomeric amines which were separated by crystallization of the HCI salts giving 5-a-methyl-3-methoxy-5,6,7,8,9,11 a, 12-octahydro-5,11 -methanobenzo-cyclodecen-13p-amine, which is finally cleaved with concentrated HBr. 

These may be prepared by reduction of appropriate nitro compounds. The free amines are unstable, but can be isolated as the tin(IV) chloride double salts, and give stable acetyl derivatives. 2-Acetamidothiophene has been prepared by a Beckmann rearrangement of the oxime of 2-acetylthiophene (63AHC(l)l). 2-Aminothiophene hydrochloride was isolated in 84% yield when cw-4-benzhydrylthiocrotononitrile was treated with hydrogen chloride gas in dry ether (equation 46) (69JHC147). 

In an alternate procedure, the last step is carried out in acetonitrile using the same quantities. During the addition of the diamine, the solution is maintained at 5°C, allowed to rise slowly to room temperature for about 15 min, and then warmed to about 75°C for one-half hour. ( Caution. The temperature must be monitored closely since the reaction is strongly exothermic.) The relatively pure amine oxime hydrochloride (PnAO 2HC1) is collected on a filter and washed with 50-mL portions of acetonitrile and dried in air. 

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